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We report on a patient with trisomy 18 syndrome and tetrasomy 18p. The case indicates that the presence of an isochromosome i(18p) can mimic complete trisomy 18 syndrome.

Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C3H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of 125IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected. These results suggest that resistance to T cell-depleted allogeneic bone marrow in irradiated mice closely correlates with the frequencies of residual host clonable T cells detectable by conventional immunologic assays.

Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.

The clinical course and outcome of 31 women suffering from breast carcinoma with documented pleural involvement was reviewed retrospectively. These 31 patients represent 14% of all patients with metastatic breast cancer seen in our Institution between 1977 and 1982. Most effusions were unilateral and ipsilateral to the affected breast, and the median interval from diagnosis of breast cancer to detection of pleural effusion was 32 months (range 0 to 84). In 55% of the patients, the effusion represented the first site of failure; in patients with known metastatic disease, the median interval from initial failure to the development of pleural effusion was 12 months. Local recurrence in the affected breast or chest wall very frequently preceded the onset of an ipsilateral effusion. Once pleural fluid developed, spread to other visceral organs was common. Treatment regimens were far from uniform and included systemic chemotherapy, hormone therapy or both, as well as intrapleural treatment; 10 of 22 patients (45%) given any form of therapy other than thoracentesis had a significant decrease in the amount of the effusion, including 3 patients with a complete response. The median survival of all patients from the onset of the effusion was 7 months (1-72); complete responders survived a median of 15 months whereas progressors had a median survival of 5 months only. Prognostic characteristics associated with a prolonged survival were: a unilateral effusion, ipsilateral to the primary tumor; effusion as first site of relapse, and mainly, an objective response to therapy. Although this is a small series, patients given both systemic and intracavitary treatment achieved best results.(ABSTRACT TRUNCATED AT 250 WORDS)

C3H/HeJ mice were exposed to 8 or 9 Gy total body irradiation prior to transplantation of 1-15 x 10(6) H-2 incompatible T cell-depleted bone marrow cells from C57BL/6 donors. Survival was greatly enhanced compared to irradiated controls, even at the lowest cell doses. Analysis of spleen cells 1-7 weeks post-transplant revealed that recipients of the lowest doses of T cell-depleted bone marrow had only transient engraftment of donor type cells, and that long-term recovery was autologous. This transient engraftment had a marked beneficial effect both on reconstitution of hematopoiesis and on survival.